Abstract

IntroductionPatients surviving a severe stroke are at risk of developing contractures. Evidence suggests that spasticity may be a cause of contractures, particularly in patients who have not recovered functional movement. The relationship and the time course of spasticity and contractures remain unclear.This thesis aims to identify when spasticity can be identified and investigate whether treating spasticity at onset using botulinum-toxin, might slow contracture development.

MethodsA double blind randomised placebo-controlled trial with an initial six-week screening phase was conducted in an acute NHS hospital.Patients with no arm function (Action Research Arm Test grasp-score<2) within six-weeks of stroke were eligible for screening. Screening for spasticity was carried out using a neurophysiological method. Patients who developed spasticity were randomly assigned to receive intra-muscular injections of 0.9%sodium chloride solution or onabotulinumtoxinA.Measures of spasticity and contracture development (reduced passive range of motion (PROM) and increased stiffness) were taken at the wrist and elbow at baseline, weeks-two, four, six and twelve post injection and six-months post stroke.

ResultsOver a 23-month period, 1143 patients were admitted with stroke and 120 consented to study participation. Of these, 100 developed spasticity without functional recovery 84%(95% confidence interval(95%CI):76%-89%). Mean time of spasticity onset was 13.5-days(SD:8.5).Of the 100 eligible for randomisation 93 were included in intention to treat analysis. At six-weeks, treatment results in a reduction in wrist spasticity (mean difference(MD):4.8μV;95%CI:1.2to8.4;p=0.009), stiffness (MD=4.2mN/deg;95%CI:0.7to7.7;p=0.02) and PROM (MD=13.8o;95%CI:6.1to21.6;p=0.01). At the elbow; four-weeks spasticity (MD=9.8μV;95%CI:4.3to15.4;p=0.001), four-week stiffness (MD=4.8mN/deg;95%CI:-0.1to9.6;p=0.056) and twelve-weeks PROM–(MD=6.5o;95%CI:0.6to12.3;p=0.03). These changes were not maintained at the six-month follow-up assessment.

ConclusionSpasticity occurs earlier and is more common than previously reported. Treating spasticity early with onabotulinumtoxinA can reduce the rate of contracture formation. Further work is required to elucidate who is at greatest risk of contractures and to explore if these treatment effects can be sustained with adjunct therapies.